Spatial transcriptomic studies are becoming increasingly common and large, posing important statistical and computational challenges for many analytic tasks. Here, we present SPARK-X, a non-parametric method for rapid and effective detection of spatially expressed genes in large spatial transcriptomic studies.
SPARK-X not only produces effective type I error control and high power but also brings orders of magnitude computational savings. We apply SPARK-X to analyze three large datasets, one of which is only analyzable by SPARK-X. In these data, SPARK-X identifies many spatially expressed genes including those that are spatially expressed within the same cell type, revealing new biological insights.
Charting an organs’ biological atlas requires us to spatially resolve the entire single-cell transcriptome, and to relate such cellular features to the anatomical scale. Single-cell and single-nucleus RNA-seq (sc/snRNA-seq) can profile cells comprehensively, but lose spatial information.
Spatial transcriptomics allows for spatial measurements, but at lower resolution and with limited sensitivity. Targeted in situ technologies solve both issues, but are limited in gene throughput. To overcome these limitations we present Tangram, a method that aligns sc/snRNA-seq data to various forms of spatial data collected from the same region, including MERFISH, STARmap, smFISH, Spatial Transcriptomics (Visium) and histological images.
**Tangram** can map any type of sc/snRNA-seq data, including multimodal data such as those from SHARE-seq, which we used to reveal spatial patterns of chromatin accessibility. We demonstrate Tangram on healthy mouse brain tissue, by reconstructing a genome-wide anatomically integrated spatial map at single-cell resolution of the visual and somatomotor areas.
Single-cell RNA sequencing (scRNA-seq) data have allowed us to investigate cellular heterogeneity and the kinetics of a biological process. Some studies need to understand how cells change state, and corresponding genes during the process, but it is challenging to track the cell development in scRNA-seq protocols. Therefore, a variety of statistical and computational methods have been proposed for lineage inference (or pseudotemporal ordering) to reconstruct the states of cells according to the developmental process from the measured snapshot data. Specifically, lineage refers to an ordered transition of cellular states, where individual cells represent points along. pseudotime is a one-dimensional variable representing each cell’s transcriptional progression toward the terminal state.
Slingshot which is one of the methods suggested for lineage reconstruction and pseudotime inference from single-cell gene expression data. In this notebook, we will illustrate an example workflow for cell lineage and pseudotime inference using Slingshot. The notebook is inspired by Slingshot's vignette and modified to demonstrate how the tool works on BioTuring's platform.
Build single-cell trajectories with the software that introduced **pseudotime**. Find out about cell fate decisions and the genes regulated as they're made.
Group and classify your cells based on gene expression. Identify new cell types and states and the genes that distinguish them.
Find genes that vary between cell types and states, over trajectories, or in response to perturbations using statistically robust, flexible differential analysis.
In development, disease, and throughout life, cells transition from one state to another. Monocle introduced the concept of **pseudotime**, which is a measure of how far a cell has moved through biological progress.
Many researchers are using single-cell RNA-Seq to discover new cell types. Monocle 3 can help you purify them or characterize them further by identifying key marker genes that you can use in follow-up experiments such as immunofluorescence or flow sorting.
**Single-cell trajectory analysis** shows how cells choose between one of several possible end states. The new reconstruction algorithms introduced in Monocle 3 can robustly reveal branching trajectories, along with the genes that cells use to navigate these decisions.
CellTypist is an automated cell type annotation tool for scRNA-seq datasets on the basis of logistic regression classifiers optimised by the stochastic gradient descent algorithm. CellTypist allows for cell prediction using either built-in (with a current focus on immune sub-populations)or custom models, in order to assist in the accurate classification of different cell types and subtypes.
CellTypist can identify 101 cell types or states from more than one million cells, including previously underappreciated cell states.
For the CellTypist pre-trained models, immune cells from 20 tissues of 19 studies were collected and harmonized into consistent labels. These cells were split into equal-sized mini-batches, and these batches were sequentially trained by the l2-regularized logistic regression using stochastic gradient descent learning. Feature selection was performed to choose the top 300 genes from each cell type, and the union of these genes was supplied as the input for a second round of training.